Fig. 7

Enhanced NHEJ-Dependent DNA repair and chemoresistance in pancreatic cancer in vivo induced by CAF-derived EV-delivered circBIRC6. (A) Schematic representation of the orthotopic xenograft model establishment process. Panc-1 cells, transfected with either XRCC4^WT or XRCC4^K115R mutation, were injected into the pancreas of nude mice. Post-implantation (12 days), mice underwent distinct treatments at intervals indicated by colored arrows. (B-C) Display of representative IVIS images (B) and harvested pancreatic tumors (C) from the orthotopic xenograft model (n = 5 mice per group). (D-E) Quantification of the luminescence intensity (D) and volumetric assessment of the tumor (E) in the orthotopic xenograft model. (F) Illustrative images of immunohistochemical staining for γH2AX and TUNEL in the orthotopic xenograft model. Scale bars equate to 100 μm. (G) A chronological schematic for the mice treatment in the Patient-Derived Xenograft (PDX) model, with colored arrows representing various treatment time points. (H) Depiction of tumor growth curves (n = 5 mice per group). (I) Exhibiting representative images of immunohistochemical staining for γH2AX and TUNEL in the PDX model. Scale bars equate to 100 μm. Data are presented as mean ± SD. n.s., not significant. ***p < 0.001